Influence of mistletoe lectins and cytokines induced by them on cell proliferation of human melanoma cells in vitro

Thies, Anka; Nugel, Dirk; Pfüller, Uwe; Moll, Ingrid; Schumacher, Udo

doi:10.1016/j.tox.2004.09.009

Cited by 54 publications

(41 citation statements)

References 38 publications

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“…The strongest cytotoxic effect was noted at low-dose ML-I (30 ng kg À1 ), where apoptosis rates were increase by a factor of 2.6 over the vehicle control (Po0.0001). Primary tumours in the groups with higher doses also showed increased apoptosis rates (factor 1.7 (150 ng kg À1 ) and 1.8 (500 ng kg À1 ); Po0.01); however, apoptosis rates did not increase in parallel to increased ML-I concentrations as one would have expected from our in vitro data (Thies et al, 2005). As no significant reduction in tumour weight was noted in the two groups with higher ML-I doses, the direct cytotoxic effect of ML-I seems to play only a minor role in its antitumorigenic effect in vivo.…”

Section: Discussionsupporting

confidence: 48%

“…Purified ML-I was used, as a strong antiproliferative effect on a number of human melanoma cell lines, due to the induction of apoptosis, has already been demonstrated in vitro (Thies et al, 2005). The human melanoma cell line MV3 was used to model a targeted therapy in vivo, since MV3 cells expressed high numbers of ML-I-binding sites and proved to be ultrasensitive to ML-I cytotoxicity in vitro (Thies et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…As both metastatic primary malignant melanomas and their metastases express particularly high numbers of ML-I binding sites, malignant melanoma cells represent an ideal target for ML-I cytotoxic therapy (Thies et al, 2001(Thies et al, , 2007a. Previous in vitro experiments have already demonstrated a highly significant antiproliferative effect of ML-I on malignant melanoma cells, which is due to the induction of apoptosis (Thies et al, 2005). In addition to its cytotoxic effect, ML-I might have further impact on tumour growth and metastases through its stimulation of the immune system, raising the number and the activity of NK cells, dendritic cells (DCs) and granulocytes (Hajto et al, 1997;Pryme et al, 2006).…”

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confidence: 99%

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Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model

et al. 2007

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This study investigates the effects of mistletoe lectin-I (ML-I) on melanoma growth and spread in vivo. The human melanoma cell line MV3 was xenografted into severe combined immunodeficient mice and vehicle solution or purified ML-I was administered at 30, 150 and 500 ng per kg body weight (20 mice per group) daily. After 19 days, mice were killed, primary tumours (PTs) and lungs were dissected out, and tumour weights, number of lung metastases (LMs), number of tumour-infiltrating dendritic cells (DCs), and apoptosis rates in the melanoma cells and in the DCs were assessed. A 35% reduction of PT weight (P ¼ 0.03) and a 55% decrease in number of LMs (P ¼ 0.016) were evident for low-dose ML-I (30 ng kg À1 ) treatment but not for higher doses. Mistletoe lectin-I increased apoptosis rates in the melanoma cells of PTs at all doses, while no induction of apoptosis was noted in the LMs. Low-dose ML-I significantly increased the number of DCs infiltrating the PTs (Po0.0001) and protected DCs against apoptosis, while higher doses induced apoptosis in the DCs (Po0.01). Our results demonstrate that low-dose ML-I reduced melanoma growth and number of metastases in vivo, primarily due to immunomodulatory effects.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model

et al. 2007

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“…Numerous studies have examined the effects of lectins on cancer cells (Minko, 2003;Valentiner, et al 2002;2003, Bangchonglikitbul, 2002Lorea, et al, 1997;Lityńska, et al 2001;Schwarz, et al 1999) and some studies report use of lectins in supplemental cancer therapy in humans (Fritz, et al, 2004;Thies, et al, 2005). Few studies have screened cancer cells and their normal counterparts for binding compounds such as lectins in order to determine if compounds can be identified that differentially bind to cancer cells and minimally to their normal counterparts (Bakalova and Ohba, 2003;Heinrich, et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Analysis of unconventional approaches for the rapid detection of surface lectin binding ligands on human cell lines

et al. 2006

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SummaryThis laboratory has developed and used a novel histochemical assay using derivatized agarose beads for over a decade to examine the surface properties of various cell types. Most recently we have used this assay to examine lectin binding ligands on two human cell types, CCL-220, a colon cancer cell line, and CRL-1459, a non-cancer colon cell line. We found that CCL-220 cells bound specific lectins better than CRL-1459, and this information was used to test for possible differential toxicity of these lectins in culture, as a possible approach in the design of more specific anti-cancer drugs. Although we have examined the validity of the bead-binding assay in sea urchin cell systems, we have not validated this technique for mammalian cells. Here the binding results of the bead assay are compared with conventional fluorescence assays, using lectins from 3 species (Triticum vulgaris, Phaseolus vulgaris, and Lens culinaris) on the 2 colon cell lines. These lectins were chosen because they seemed to interact with the two cell lines differently.Binding results obtained using both assays were compared for frozen, thawed and fixed; cultured and fixed; and live cells. Both qualitative and quantitative fluorescence results generally correlated with those using the bead assay. Similar results were also obtained with all of the 3 different cell preparation protocols. The fluorescence assay was able to detect lower lectin binding ligand levels than the bead assay, while the bead assay, because it can so rapidly detect cells with large numbers of lectin binding ligands, is ideal for initial screening studies that seek to identify cells that are rich in surface binders for specific molecules. The direct use of frozen, thawed, and fixed cells allows rapid mass screening for surface molecules, without the requirement for costly and time consuming cell culture.

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“…Thies et al 2005 examined binding differences of three mistletoe lectins when six different melanoma cell lines were either unfixed, fixed in methanol or fixed in paraformaldehyde. Some cell lines showed a difference in binding intensity which was dependent upon whether the cells were fixed or not and which fixative was used.…”

Section: Discussionmentioning

confidence: 99%

Direct targeting of cancer cells: A multiparameter approach

et al. 2005

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SUMMARYLectins have been widely used in cell surface studies and in the development of potential anti-cancer drugs. Many past studies that have examined lectin toxicity have only evaluated the effects on cancer cells, not their non-cancer counterparts. In addition, few past studies have evaluated the relationship between lectin-cell binding and lectin toxicity on both cell types. Here we examine these parameters in one study: lectin-cell binding and lectin toxicity with both cancer cells and their normal counterparts. We found that the human colon cancer cell line CCL-220/Colo320DM bound to agarose beads derivatized with Phaseolus vulgaris agglutinin (PHA-L) and wheat germ agglutinin (WGA), while the non-cancer human colon cell line CRL-1459/CCD-18Co did not. When these lectins were tested for their effects on cell viability in culture, both cell lines were affected by the lectins but at 6, 48 and 72 hours incubation times, PHA-L was most toxic to the cancer cell line in a concentration dependent manner. At 48 hours incubation, WGA was more toxic to the cancer cell line. The results suggest that it may be possible to develop lectin protocols that selectively target cancer cells for death. In any case, examination of both malignant cells and their non-malignant counterparts, analysis of their binding characteristics to immobilized lectins, and examination of the toxicity of free lectins in culture, provides a multiparameter model for obtaining more comprehensive information than from more limited approaches. KeywordsImmobilized lectin binding; lectin toxicity in culture; human colon cancer and non-cancer colon cells; PHA-L; WGA

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Influence of mistletoe lectins and cytokines induced by them on cell proliferation of human melanoma cells in vitro

Cited by 54 publications

References 38 publications

Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model

Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model

Analysis of unconventional approaches for the rapid detection of surface lectin binding ligands on human cell lines

Direct targeting of cancer cells: A multiparameter approach

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